This project will evaluate a component of human neuroendocrine function that may reflect a biological basis for atypical sexual behavior and orientation. Adult human females, when administered either the conjugated estrogen preparation Premarin, or estradiol, show an enhanced release of luteinizing hormone (LH) from the pituitary gland. This release, stemming from estrogen stimulation to the hypothalamus, is the "positive feedback estrogen phenomenon". Males typically do not show such an enhanced LH surge. This sex-typed response may be due to a prenatal organizing event that may be related to postnatal sex-typed behaviors. If human psychosexual behavior, such as sexual orientation (sex of erotic partners) or the wish to be of the other sex (transsexualism) is related to differences in neuroendocrine development, then neuroendocrine responses to hormone challenge may be a biological marker for the degree of sex-specific brain differentiation. A recent provocative report states that male homosexuals and transsexuals exhibit a "female-type" neuroendocrine LH response pattern differing from male heterosexuals. These observations, while intriguing, are fraught with methodological flaws. However, they form the basis for an emerging theory of a biological basis for homosexuality and transsexualism. Because of the significance of this line of research related to human neuroendocrine differentiation and psychosexual orientation, an expanded, carefully conducted replication of these studies of imperative. Homosexual, heterosexual, and transsexual males, as well as heterosexual females, will be measured for changes in blood levels of LH after Premarin challenge. A positive feedback response to estrogen in males would be evidence for a atypical neuroendocrine system possibly reflecting atypical prenatal sexual differentiation. It may be useful in the search for "biological markers", particularly in the diagnosis of transsexualixm, a diagnosis that remains highly controversial. A finding of a positive feedback response in male homosexuals would suggest a biological distinction between homosexual and heterosexual men, and would suggest, but not prove, a biological component in the origins of homosexual development. Failure to demonstrate other than a genetic sex (male vs. female) difference in the neuroendocrine response would argue against this current theory of the biological basis of male homosexuality and the related suggested "prophylactic treatment" of the "high risk" male fetus with androgen.